The nonciliated bronchiolar secretory (Clara) cell may have potential importance in the manifestation of clinical diseases such as chronic bronchitis. Together with the remarkable specificity and toxicity exhibited by two furan-containing compounds, 4-ipomeanol and 3-methylfuran for this cell type, it occurred to us that further proof of the significance of the Clara Cell would be gained by correlating Clara Cell damage with changes in pulmonary function as determined by non-invasive pulmonary function tests. While the Clara Cell specificity of these pulmonary toxins has been demonstrated, nothing is known of their central nervous system or systemic effects in the in vivo situation. To avoid this complication in our studies we intend to use an isolated, perfused lung. This particular system is also especially adapted for measurements of pulmonary function. The significance of the Clara Cell has been heightened by the finding that this cell type may serve as a site of drug metabolism in the lung. Thus, damage to or destruction of this cell type may severely compromise the ability of the lung to detoxify xenobiotics thereby resulting in enhanced lung or systemic toxicity. Since the lung is also capable of metabolically activating some carcinogens, any process affecting this biotransformation should be assessed. For these reasons, the cytochrome(s)-P-450-linked mixed-function oxidase activity in the lung (and in some cases the liver) will be measured using known substrates of the mixed function oxidase system. The selective destruction of the Clara Cell and other changes in lung cell integrity and population will be monitored using light microscopy to examine the parenchymal and nonparenchymal cells of the lung. More subtle changes will be detected using scanning electron microscopy. Experiments will be carried out in vivo and in vitro using the rabbit as an animal model. By using radiolabeled 4-ipomeanol and 3-methylfuran we intend to study the uptake, distribution and metabolism of these compounds will be administered in vivo and autoradiograms of the lung tissue prepared in order to further determine the site(s) of localization of the radioactivity within the lung.